Articular cartilage is a hydrated and lubricated joint tissue that allows for the relative movement of opposing joint surfaces under high loads (Scholten et al. (2011): Buckwalter et al. (1998); Mow et al. (1993)). Mature articular cartilage does not possess an intrinsic ability to heal, since it is avascular and lacks a source of mesenchymal cells (Scholten et al. (2010); Buckwalter et al. (1998)).
Current operative procedures for the treatment of articular cartilage damage generally fall into four categories: 1. nontransplant salvage operations such as abrasion arthroplasty; 2. mosaicplasty in which a cartilage-bone plug is transplanted into a joint which is minimally weight bearing; 3. reimplantation of autogenously isolated and expanded cells; and 4. the implantation of allografts (Maher et al. (2007); Szerb et al. (2005); Freedman et al. (2003); Brittburg et al. (2003); Gross (2003)). However, all of these techniques have their limitations, and do not prevent the progression of the osteoarthritis, which often propagates from the focal defect. Furthermore, over 33% of those affected by arthritis are under age 65. Accordingly, the number of young patients with total knee replacement, the end stage treatment for arthritis, is increasing. Performance of joint replacements in younger patient populations is less satisfactory than for older patients, oftentimes leading to multiple revision surgeries, each with successively diminishing longevity.
One proposed method for an alternative treatment is the use of a non-degradable synthetic non-cell derived implant to stabilize a chondral defect, thereby protecting adjacent tissue from degradation. Ideally, the scaffold would carry and distribute load similarly to native tissue, and also provide a mechanism for long-term fixation (Scholten et al. (2011)). While non-degradable hydrogel scaffolds (hydrophilic, crosslinked, hydrated polymeric networks), such as those made from poly(vinyl) alcohol (PVA), have shown to be promising in in vivo animal studies (Noguchi et al. (1991); Oka et al. (1990)), many have failed due to the lack of a porous periphery which would be required to facilitate cell migration and integration (Maher et al. (2007); Swieszkowski et al. (2006); Stammen et al. (2001)). Additionally, the mechanical properties of the scaffolds developed thus far are unable to carry joint loads of native tissue at the time of implantation (Maher et al. (2007)).
Moreover, the techniques developed thus far for creating porous PVA scaffolds either do not enable control over the mechanical properties of the end-product or do not enable the formation of a truly interconnected porous network. For example, one technique created a hybrid cellulose-PVA scaffold, intended to enable ultra-filtration and dialysis for biohybrid artificial organs. However, this method of manufacture did not enable control over the mechanical properties, nor control over porosity (Dai et al. (2000)). Previous studies have utilized PVA mixed with other compounds to form a porous PVA construct. One technique mixed polyethylene glycol (PEG) with polyvinyl alcohol. The binary solution was designed such that the PEG does not gel with freeze-thawing of the PVA and is responsible for the resulting porous network. PEG is then washed out and replaced with water (Bodugoz-Senturk et al. 2008). Another technique involved mixing polyacryl amide with polyvinyl alcohol (Bodugoz-Senturk et al. 2009). The solution is then gelled in order to structurally reinforce the porous network formed within the PVA. These porous PVA constructs have been shown to support cellular activity (Bichara et al.), but the pores only appear to be partially interconnected, with many pores appearing to be bubbles of fluid. Moreover, control over the mechanical properties and the porosity is not possible using the aforementioned techniques.
Therefore, there is a need in the art for a more reliable method to treat patients with chondral defects, especially young active ones, early in the course of the problem, thus delaying or eliminating the need for total joint replacement, and a real need in the art for a process for manufacturing PVA scaffolds where there is precise control over the mechanical properties and porosity of the resulting scaffold.